Hemodialysis apparatus

ABSTRACT

A hemodialysis apparatus includes means for measuring or calculating a blood volume or a blood volume change as a blood index level, a hemodialysis means, and a controlling means that controls hemodialysis conditions of the hemodialysis means according to the blood index level. The controlling means controls the hemodialysis means so that hemodialysis operation is carried out without performing water removal at the time of the initiation of the hemodialysis operation until the blood volume stabilizes. The hemodialysis operation is carried out by performing water removal after the blood volume is stabilized by the hemodialysis operation without performing water removal, and that is a constitution so that it is possible to calculate the primary blood volume (BV 0 ) of each patient according to the following formula (I), from % ΔBV of hemodialysis operation which has been carried out before the blood volume is stabilized, and the increased blood volume circulating outside the body. The primary blood volume (BV 0 )=increased blood volume circulating outside the body (space outside the body)/% ΔBV x . (I), wherein % ΔBV x  is the ratio of the volume change of the blood volume (BV) when hemodialysis is performed without performing water removal.

TECHNICAL FIELD

The present invention relates to a blood treatment apparatus, especiallyto a hemodialysis apparatus which can control water removal conditionsand water removal speed so as to prevent excessive water removal andalso lack of water removal in the contrary, which occur frequentlyduring hemodialysis.

BACKGROUND ART

For treating patients with impaired kidney function, treatments bypurifying blood by dialysis or filtration via semipermeable membranehave been provided conventionally. As for this apparatus, it isimportant to appropriately maintain the blood volume circulating in thepatient body, to perform safe and effective blood purification. A rapidor excessive water removal will decrease excessively patient's bloodcirculating volume, and it may cause reduction of blood pressure, shockor the like. On the contrary, if the water removal is slow, it will takea long time for blood purification, and if sufficient water removalcannot be made, there is a fear that hypertension, heart failure or thelike can occur. Therefore, a hemodialysis apparatus performing waterremoval by monitoring patient's blood condition has been developed. Forexample, in Japanese Laid-Open Patent Publication No. 6-83723, anestimating apparatus which estimates the body fluid condition with aHematocrit meter, and a controlling apparatus which controls the bloodpump or ultra pressure by the output of said estimating apparatus aredescribed. Concerning this apparatus, it is convenient as the waterremoval is controlled directly according to the measured body fluidcondition, but on the other hand, as the water removal is controlleddirectly by the measured value, in case the result of the measuringmeans is not accurate or a trouble happens, it may cause a significantproblem. Therefore, in such feed-forward control, generally, a separateline independent from the control line is disposed and a safetymechanism is loaded on said line. However, the apparatus becomescomplicated when an independent line or safety mechanism is disposed andthe operation becomes difficult. Furthermore, the cost of the apparatuswill rise. Therefore, a simple apparatus as described in JapaneseLaid-Open Patent Application No. 9-149935 was also developed. In otherwords, while monitoring the patient's blood condition, an alarm isringed depending to the condition, and the water removal pump isstopped. However, this apparatus only recognizes if the water removalcontrol is performed under the same control condition at the time of theinitiation of dialysis, by comparing with the blood concentrationmeasured before the initiation of dialysis, and it is not possible toperform adequate water removal to each patent. Furthermore, if the waterremoval is not performed according to the condition, the operator has toadjust each time the water removal volume or fluid replacement volume.Thus, even though it was safe, it was complicated and the human cost washigh. Moreover, as for said apparatus, a means for measuring the bloodcondition is disposed on the line at the vein fluid side of the bloodcycle, the blood condition after having passed the blood treatmentmachine (dialyser) is measured, thus it may not reflect the patient'sdirect blood condition.

To provide a blood treatment apparatus which have solved the problemsmentioned above, that is, to provide a convenient apparatus at a lowcost by making a structure wherein each patient's blood condition ismonitored, enabling to perform blood treatment adequate to each patientchronologically, by not imposing much burden to the operator during itsuse, and by making the construction of the blood treatment apparatussimple, the present inventors provided a blood treatment apparatus(Japanese Laid-Open Patent Application No. 11-22175), comprising a bloodmeasuring means for measuring blood parameters; a working unit forperforming blood treatment; and a controlling unit controlling theworking unit to perform blood treatment under prescribed blood treatmentcondition, wherein the controlling unit indicates the change of theblood treatment condition to the working unit, by setting a bloodindication region determined beforehand against the patient bloodindication level obtained with said blood measuring means, according tothe chronological transition of said blood indication level in saidblood indication region. Furthermore, the present inventors haveimproved said blood treatment apparatus (Japanese Laid-Open PatentApplication No. 11-22175), and proposed a blood treatment apparatus(Japanese Laid-Open Patent Application No. 2001-540), wherein bymonitoring each patient's blood condition, the condition of hemodialysisadequate to each patient chronologically, especially the water removalspeed can be easily changed and defined. Said blood treatment apparatus(Japanese Laid-Open Patent Application No. 2001-540) is a hemodialysisapparatus comprising at least:(A) a blood measuring means for measuringblood parameter, (B) a working unit for performing blood treatment; and(C) a controlling unit for controlling the working unit to perform bloodtreatment under prescribed blood treatment condition; wherein thehemodialysis apparatus has a mechanism for controlling the water removalspeed, and the controlling unit (C) incorporates the blood indicatinglevel obtained from the patients' samples by the blood measuring means(A), monitoring if it transits or not within the defined range definedbeforehand of blood indication level (hereinafter also referred to asdefined range of blood indication level), and when said blood indicationlevel being the target to control deviates from said range definedbeforehand, the water removal speed of the working unit (B) can bechanged at a speed rate defined beforehand.

As for the hemodialysis apparatus mentioned above, it was possible tomanage surely the blood indication level at each point duringhemodialysis treatment, but because it was necessary to define theregion of the target blood indication level at each point, the operationwas complicated. Furthermore, as the defined blood indication level wasdesignated as a range, as long as a blood indication level exists withinthe defined range, even it is at the absolute edge of the range, thecontrol mechanism of the hemodialysis apparatus would not work.Therefore, in case the blood indication level actually measured isslightly missing the point from the target, there was a fear that thecontrol would be delayed. Furthermore, as for said apparatus, minutedetails were defined in each region, and the control is carried outaccording to these, the physiological water removal adequate to eachpatient was difficult to be carried out. On the contrary, when the waterremoval mild to the living body is intended to be carried out, ithappened that the water removal volume which was determined beforehand,can not be attained.

DISCLOSURE OF THE INVENTION

The object of the present invention is to provide a hemodialysisapparatus that can achieve the following effects:

-   (1) The control mechanism is simple, and there is little risk of    misoperation or out-of-control.-   (2) As there is no need of difficult installation or unnecessary    operation, the operator can easily operate without difficulty.-   (3) As the control is carried out rapidly and finely, the blood    volume can be transited fairly during the hemodialysis.

The present invention provides a hemodialysis apparatus having a meansfor measuring or calculating a blood volume or a blood volume change asa blood index level, a hemodialysis means, and a controlling means thatcontrols hemodialysis conditions of the hemodialysis means according tothe blood index level, wherein the controlling means controls thehemodialysis means to perform hemodialysis operation without performingwater removal until the blood volume stabilizes, at the initiation ofhemodialysis operation, and then to perform hemodialysis operation byperforming water removal after the blood volume is stabilized by thehemodialysis operation without water removal, and which is constitutedso that it is possible to calculate the primary blood volume of eachpatient (BV₀) according to the following formula (I) or (II).

1. Calculation of the primary blood volume (BV₀) according to formula(I)

The first calculation method of the primary blood volume (BV0) isexplained according to FIG. 3.

At the time of the initiation of hemodialysis, as the blood volume isnot stable, when performing hemodialysis without performing waterremoval the turgor pressure inside the cells is sufficiently high, andthe water runs over from cells to intercellular substances, it isbelieved that water corresponding to the increased blood circulatingspace of the hemodialysis apparatus will move from the cells to theblood vessel. Therefore, it is possible to obtain the primary bloodvolume (BV₀) of each patient, according to the following formula (I)with the increased blood circulating space of the hemodialysis apparatusand % ΔBV_(x). Primary blood volume (BV₀)=increased blood circulatingspace of the hemodialysis apparatus /% ΔBV_(x) . . . (I) [wherein %ΔBV_(x) is the ratio of the volume change of the blood volume (BV) whenhemodialysis is performed without performing water removal]

(2) Calculation of the primary blood volume (BV₀) according to (II)

The second calculation method of the primary blood volume (BV0) isexplained according to FIG. 4.

At the time of the initiation of hemodialysis, hemodialysis is performedwithout water removal until the blood volume stabilizes, and when theblood volume (BV) level becomes stable, hemodialysis accompanied bywater removal is initiated, and at the same time as said hemodialysis isinitiated, the water removal is performed with a certain time ΔT (withinthe time PRR does not change), and with a certain water removal speed(water removal speed A), and thus ΔBV_(A), which is the volume change ofthe blood volume (BV) is calculated. Then, the water removal isperformed for the same time as said certain time ΔT with a differentwater removal speed (water removal speed B), and thus, ΔBV_(B) which isthe volume change of said BV level, is calculated. Thus, BV₀ can becalculated by using said ΔBV_(A), said ΔBV_(B), water removal speed Aand water removal speed B, according to the following formula (II).BV ₀=(water removal speed A−water removal speed B)/(−ΔBV _(A) %+ΔBV _(B)%)×ΔT  (II)Said formula (II) can be calculated as follows.ΔBV/ΔT=PRR−UFR−ΔBV _(A) /ΔT+ΔBV _(B) /ΔT=water removal speed A−water removal speed BBV _(A) =ΔBV ₀·% ΔBV _(A)ΔBV _(B) =ΔBV ₀·% ΔBV _(B)BV ₀ /ΔT(−% ΔBV _(A)+% ΔBV _(B))=water removal speed A−water removalspeed BBV ₀ /ΔT=(water removal speed A−water removal speed B)/(−% ΔBV _(A)+%ΔBV _(B))

In the meantime, the calculating method of said primary blood volume(BV₀) of the present invention is, as it is clear from its calculatingmethod, widely acceptable as long as it is a hemodialysis apparatus thatcarries out hemodialysis treatment by controlling the dialysis conditionaccording to said blood indication level, being the blood volume or itschanging parameter.

As for the hemodialysis apparatus of the present invention, it ispossible to carry out control with the use of blood indication level,wherein the target BV % is calculated automatically according to thefollowing formula with the use of the primary blood volume (BV₀) of eachpatient calculated as mentioned above, and the standard blood volume (BVst) which is defined beforehand by doctors and the like.Target BV %=standard blood volume(BV st)/primary blood volume(BV ₀)×100Meanwhile, said standard blood volume (BV st) is a level of the bloodvolume (BV st) which the patient would have if healthy, definedbeforehand by doctors and the like by considering factors that mightinfluence the human blood volume, for example the patient's age, sex,body height and the like.

Definition of the blood indication level being the blood volume or itschanging parameter and its calculating formula used in the hemodialysisapparatus of the present invention

(1) BV volume (BV)

BV is the abbreviation of Blood Volume level and is the circulatingblood volume index which is the indication level to check the conditionof the circulating blood volume of each patient.

(2)ΔBV level

It is the BV volume change, and it is calculated by the followingformula.ΔBV=(Ht at the time of the initiation of hemodialysis/Ht at the time ofmeasurement)−1

Said Ht is the abbreviation of Hematocrit showing the bulk ratio of redcorpuscle in the whole blood.

(3) % ΔBV

It is the ratio of the blood volume change, and as shown in thefollowing formula, the ΔBV level at the time of measurement is dividedby BV₀ which is the BV level at the time of the initiation of dialysisand is expressed in percentage.ΔBV %=ΔBV/BV ₀×100(4) BV %

It is calculated by dividing the BV level at the time of measurement byBV₀ at the time of the initiation of hemodialysis and is expressed inpercentage.BV %=BV level at the time of measurement/BV ₀×1003. Definition of other parameters of blood and their calculating formula(1) Definition of PRR

PRR is an abbreviation for Plasma Refilling Rate, and is defined asspeed of the blood plasma refilling from the body to the blood vessel,and shows the patient's water removal ability at each point.

(2) Formula for calculating PRR

PPR is calculated with the following formula:PRR _(n) −UFR _(n) =ΔBV _(n) /T _(n)[wherein PRR_(n) is the Plasma Refilling Rate at an optional selectedmeasurement time point (n) of the hemodialysis, UFR_(n) is the waterremoval speed at the optional selected measurement time point (n),ΔBV_(n) is the blood volume change at the measurement time point (n),T_(n) is the elapsed time until the measurement time point (n), and UFRis the water removal speed, respectively.]

The hemodialysis apparatus of the present invention can perform thehemodialysis operation with water removal by determining the bloodvolume or the blood index level being its changing parameter, at pluraltime points of the chronological course of the hemodialysis operation,and by using the control line (target control line) constituted with thedetermined blood index level.

The control of the water removal speed in the former part of thedialysis operation of the hemodialysis apparatus with the use of saidtarget control line is performed by using the blood indication levelmeasured at each measurement point; and the target blood indicationlevel showed by said target control line at the next measurement pointof each measurement point.

The control of the water removal speed in the former part of thedialysis operation of the hemodialysis apparatus with the use of saidtarget control line can be calculated according to each blood indicationlevel of two adjacent measurement points; the water removal speed usedbetween the two measurement points mentioned above; the blood indicationlevel at the time of the initiation of the hemodialysis; and the targetblood indication level determined by said target control line at thenext measurement point of the two measurement points mentioned above.

Concretely, said control can be carried out by using the followingformula (n).BV ₀{−(% ΔBV _(n−1′)−% ΔBV _(n′))+(% ΔBV _(n′)−% ΔBV _(n+1))}+UFR _(n)×T=UFR _(n+1) ×T  (n)(wherein BV₀ is the primary blood volume; % ΔBV_(n′) is the ratio of theblood volume change at an optional selected measurement time point (n);% ΔBV_(n−1′) is the ratio of the blood volume change at the previousmeasurement time point (n−1) of the selected measurement time point (n)in the former part of the dialysis operation; % ΔBV_(n+1) is the ratioof the blood volume change determined by said target control line at ameasurement time point (n+1), the next measurement time point of themeasurement time point (n); T is the measurement time; UFR_(n) is thewater removal speed at the selected blood measurement time point (n) inthe former part of the dialysis operation; and UFR_(n+1) is the waterremoval speed defined when the control toward the working unit iscarried out, to attain the target blood indication level at ameasurement time point (n+1), the next measurement point of themeasurement time point (n), respectively.)

Said formula (n) is calculated as follows:

When the BV level at the time of the initiation of hemodialysis is setas BV₀ (primary blood volume), at each measurement point in the formerpart of the hemodialysis operation, for example, relational formulae asfollows are obtained between BV level, PPR and UFR at the first andsecond measurement point.

1st Measurement PointBV ₀{(100%−% ΔBV ₁)−(100%−% ΔBV ₂)}=PRR ₁ −UFR ₁BV ₀(−% ΔBV _(1′)+% ΔBV _(2′))/T=PRR ₁ −UFR ₁  (1)2nd Measurement PointBV ₀(−% ΔBV _(2′)+% ΔBV ₃)/T=PRR ₂ −UFR ₂  (2)Here, BV₀, % ΔBV_(1′), % ΔBV_(2′) and T show the BV level at the time ofthe initiation of hemodialysis, the ratio of the BV volume change at thefirst or second measurement point and the elapsed time of dialysis,respectively. Moreover, % ΔBV₃ is determined by the target control line.

Similar relations are also obtained at each optional measurement points,(n−1) or (n), as it is shown in the following relational formulae.

(n−1)th measurement pointBV ₀(−% ΔBV _(n−1′)+% ΔBV _(n′))/T=PRR _(n−1) −UFR _(n−1)(n)th measurement pointBV ₀(−% ΔBV _(n′)+% ΔBV _(n+1))/T=PRR _(n) −UFR _(n)

By subtracting said formula (2) from said formula (1), the followingformula (3) is obtained.BV ₀{(% ΔBV _(1′)−% ΔBV _(2′))−(% ΔBV _(2′)−% ΔBV ₃)}/T=PRR ₁ −PRR ₂+UFR ₂ −UFR ₁  (3)

When it is hypothecated there is no difference between PRR₁ and PRR₂,that is the distance between the measurement points are defined to beshort so as the patient's PPR is not changed substantively at eachmeasurement point, the first and second terms in the right side aredeleted. Thus, the following formula (4) is obtained.BV ₀{−(% ΔBV _(1′)−% ΔBV _(2′))+(% ΔBV _(2′)−% ΔBV ₃)}/T+UFR ₁ =UFR₂  (4)

In this formula, % ΔBV₃ is the target level at the next measurementpoint, and is a level for the blood indication level to approach bycarrying out the control. Furthermore, UFR₂ is the water removal speedto define so that the blood indication level at the next measurementpoint approaches the target level mentioned above. Here, BV₀, %ΔBV_(1′), % ΔBV_(2′), T are well known as the BV level at the time ofthe initiation of dialysis, the ratio of the blood volume change at thefirst or second measurement point, and the elapsed time of dialysis,respectively. Moreover, UFR₁ is also well known as the water removalspeed from the first measurement point to the second measurement point.Therefore, if % ΔBV₃, which is the target ratio of the BV volume changeis specified, the water removal speed being a dialysis condition can becalculated with the formula (4). The target BV level can be determinedby the target control line, from the measurement point. On the contrary,if the hemodialysis treatment is carried out with that water removalspeed, the BV level at the next measurement point can approach thetarget level, that is the target control line.

When describing the above formula for an optional measurement point (n),of hemodialysis, it is shown as the following formula (n), and asdescribed above, the water removal speed to be defined so that the bloodindication level approaches the target at the next point is determinedby the BV volume change at the two measurement points; the water removalspeed between the two measurement points; the measurement level of thedialysis time T; and the blood indication level defined at the nextmeasurement point of the two measurement points mentioned above,determined according to the target control line of said blood indicationlevel.BV ₀{−(% ΔBV _(n−1′)−% ΔBV _(n′))+(% ΔBV _(n′)−% ΔBV _(n+1))}/T+UFR _(n)=UFR _(n+1)  (n)

In said formula, BV₀ is the primary blood volume % ΔBV_(n′) is the ratioof the blood volume change at an optional selected measurement timepoint (n) in the former part of the dialysis; % ΔBV_(n−1′) is the ratioof the blood volume change at the previous measurement point of themeasurement time point (n) % ΔBV_(n+1) is the ratio of the blood volumechange defined at a measurement time point to carry out feed-forwardcontrol; T is the measurement time; UFR_(n) is the water removal speedat the selected measurement point in the former part of the dialysisoperation; and UFR_(n+1) is the water removal speed defined at the nextmeasurement point from the selected measurement point (n) in the formerpart of the dialysis operation, when the control is carried out towardthe working unit, to attain the target blood indication level,respectively. However, to obtain said formulae (4) and (n), thecondition that “there is no difference between the PRRs at eachmeasurement point”, which was hypothecated to derive these formulae, isan assumption, and to meet this condition, it is important that thedistance between each measurement point (ΔT) is defined to be short sothat there is no difference between the PRRs. Moreover, as for thiscontrolling method, errors to the control may occur due to errors of BV₀at the time of the initiation of dialysis, control delay and otherfactors, but in the actual control, the control is ensured by definingthe water removal speed at each point (measurement point).

In other words, as for the water removal operation in the former part ofthe dialysis operation mentioned above, as it is described above, thedistance between each measurement point is defined to be short and thewater removal speed is defined each time, the errors occurringsubstantively cause no problems.

The water removal is performed by controlling the water removal speedwith a controlling means as mentioned above, and when the blood volumecirculating in the body approaches the standard blood volume, thedialysis operation of the latter part of the hemodialysis operation isstarted. When the hemodialysis operation of the latter part of thedialysis operation is started, the remaining water removal volume of thetarget water removal volume is measured or calculated, and the waterremoval speed is calculated again to finish removing said water removalvolume within the target water removal time, and the water removal ofthe latter part of the hemodialysis operation can be performed with saidwater removal speed.

As for the water removal operation of the hemodialysis apparatus of thepresent invention, it is preferable to determine beforehand the maximumwater removal speed separately for the former part of the hemodialysisoperation and the latter part of the hemodialysis operation,respectively, and when the water removal speed calculated in the formerpart or latter part of the hemodialysis operation mentioned above,exceeds said maximum water removal speed, to control so that the waterremoval is performed with said maximum water removal speed.

As for the control of the water removal operation of the hemodialysisapparatus of the present invention, it is preferable to defineseparately for the former part and the latter part of the dialysisoperation, respectively, a deviated control line (alarm line) to limitthe chronological change of the blood indication level within apredetermined range, under said target control line, and when said bloodindication level exceed said deviated control line (alarm line), tocarry out by controlling the working means that carries out thehemodialysis treatment so that the dialysis condition to recover saidblood indication level to be above said deviated control line (alarmline) is performed.

As for means to recover said blood indication level to be above saiddeviated control line (alarm line), there is means to stop temporarilythe water removal means.

In the former part of the dialysis operation, when the means to recoverthe blood indication level to be above said deviated control line (alarmline) is performed, and at the time the blood indication level isrecovered to be above said deviated control line (alarm line) as aresult, the dialysis operation is started again according to the controlof the former part of the hemodialysis operation. Furthermore, in thelatter part of the hemodialysis operation, when the means to recover theblood indication level to be above said deviated control line (alarmline) is performed, and at the time the blood indication level isrecovered to be above said deviated control line (alarm line) as aresult, the water removal speed is calculated again so that theremaining water removal volume at that time is finished to be removedwithin the target water removal time, and the hemodialysis operation ofthe latter part of the dialysis operation of the latter part of thedialysis operation is started again with said water removal speed.

Furthermore, as for the control of the water removal operation for thehemodialysis apparatus of the present invention, especially in thelatter part of the hemodialysis operation, it is preferable to enable tocontrol so that the blood indication level is recovered rapidly to beabove said deviated control line (alarm line), and in case the bloodindication level reaches downward by further exceeding said urgentsubstitutive fluid supply line, not only to stop temporarily the workingmeans that carries out blood treatment as mentioned above, but to usealso a substitutive fluid supply means to inject substitutive fluid intothe body.

Furthermore, the present inventors have found that as for the control ofthe water removal speed with the use of said target control line, thechange of the blood volume appears after the change of the water removalspeed (especially at the point when the target control line drasticallychanges). Moreover, they have found that when the feed forward controlmentioned above is carried out by ignoring said phenomenon, there is aproblem that the control is not stable, and they have proposed to solvethe problems occurred form said control delay by considering saidcontrol delay (Japanese patent application 2002-19447), to solve thisobject. However, as for means proposed above, for example means forcalculating the forecast of the dialysis condition necessary to attainthe next target blood indication level (blood volume change) accordingto the blood indication level at the point the control delay time haspassed, in the controlling method of the water removal speed using saidtarget control line, can be used when a problem of control delay asmentioned above occurs in the controlling method of the water removalspeed which uses said target control line of the present invention.

In the following, parameters concerning blood and blood indication leveland blood used in the hemodialysis apparatus of the present invention,will be explained concretely.

1. Primary Blood Volume (BV₀)

It is preferable to use the patient's inherent primary blood volume asone of the controlling factors in the former part of the dialysisoperation. Said patient's inherent primary blood volume can becalculated for example by the two following methods.

(1) The First Method for Calculating the Primary Blood Volume (BV₀)

The first method for calculating the primary blood volume (BV₀) isexplained according to FIG. 3.

At the time of the initiation of dialysis, as the blood volume is notstable, the water removal is not performed, and only circulation outsidethe body is performed. By continuing circulation outside the body untilthe blood volume stabilizes, in case the turgor pressure inside thecells is sufficiently high, and the water runs over the cells and isaccumulated up to the cell stroma, it is believed that the body fluid(the inflow volume from the cells of FIG. 3) corresponding to theincreased blood volume circulating outside the body (space outside thebody) will move from the cells to the blood vessel. Therefore, it ispossible to obtain the primary blood volume (BV₀) of each patient,according to the following formula (I) with the increased blood volumecirculating outside the body (space outside the body) and % ΔBV_(x).Primary blood volume(BV ₀)=increased blood volume circulating outsidethe body(space outside the body)/% ΔBV _(x)  (I)(% ΔBV_(x) is the ratio of the blood volume change when only circulationoutside the body is performed without performing water removal.)(2) The Second Method for Calculating the Primary Blood Volume (BV₀)

The primary blood volume (BV₀) of each patient can be obtained also bythe following method. Said second calculating method is explainedaccording to FIG. 4.

By using the hemodialysis apparatus which controls dialysis conditionsaccording to the blood indication level, only circulation outside thebody is performed without performing water removal, at the time of theinitiation of dialysis as shown in FIG. 4, said circulation outside thebody is continued until the blood volume (BV) level stabilizes, and whenthe blood volume (BV) level becomes stable, dialysis accompanied bywater removal is initiated, and at the same time as said dialysis isinitiated, the water removal is performed with a certain time ΔT (withinthe time PRR does not change), and with a certain water removal speed(water removal speed A), and thus ΔBV_(A), which is the volume change ofsaid BV level is calculated. Then, the water removal is performed forthe same time as said certain time ΔT with a different water removalspeed (water removal speed B), and thus, ΔBV_(B) which is the volumechange of said BV level, is calculated. Thus, BV₀ can be calculated byusing said ΔBV_(A), said ΔBV_(B), water removal speed A and waterremoval speed B.

The primary blood volume (BV₀) of each patient calculated by said secondmethod, can be calculated concretely according to the following formula(II).BV ₀=(water removal speed A−water removal speed B)/(−ΔBV _(A) %+ΔBV _(B)%)×ΔT  (II)Said formula can be calculated as follows. The calculating method isexplained according to FIG. 4.ΔBV/ΔT=PRR−UFR−ΔBV _(A) /ΔT+ΔBV _(B) /ΔT=water removal speed A−water removal speed BΔBV _(A) =ΔBV ₀·% ΔBV _(A)ΔBV _(B) =ΔBV ₀·% ΔBV_(B)BV ₀ /ΔT(−% ΔBV _(A)+% ΔBV _(B))=water removal speed A−water removalspeed BBV ₀ /ΔT=(water removal speed A−water removal speed B)/(−% ΔBV_(A)+%ΔBV_(B))

As for the hemodialysis apparatus of the present invention, it ispreferable that it is a constitution that enables to carry out controlwith the use of blood indication level, wherein the target BV % iscalculated automatically according to the following formula with the useof the primary blood volume (BV₀) of each patient calculated asmentioned above, and the standard blood volume (BV st) which is definedbeforehand by doctors and the like.Target BV %=standard blood volume(BV st)/primary blood volume(BV ₀)×100Meanwhile, said standard blood volume (BV st) is a level of the bloodvolume (BV st) which the patient would have if healthy, definedbeforehand by doctors and the like by considering factors that mightinfluence the human blood volume, for example the patient's age, sex,body height and the like.

In the meantime, the calculating method of said primary blood volume(BV₀) of the present invention is, as it is clear from its calculatingmethod, it is not limited to the hemodialysis apparatus controlling thewater removal operation by dividing the dialysis operation to the formerand latter part, and it is widely acceptable as long as it is ahemodialysis apparatus that carries out hemodialysis treatment bymeasuring or calculating the blood volume or its volume change as theblood indication level to control the dialysis condition according tosaid blood indication level.

2. Definition of the Blood Indication Level being the Blood Volume orits Volume Change and its Calculating Formula

(1) BV Level

BV level is the abbreviation of Blood Volume level and is thecirculating blood volume index which is the indication level to checkthe condition of the circulating blood volume of each patient.

(2) ΔBV Level

It is the BV volume change, and it is calculated by the followingformula.ΔBV[BV volume change]=(Ht at the time of the initiation of dialysis/Htat the time of measurement)−1

Said Ht is the abbreviation of Hematocrit showing the bulk ratio of redcorpuscle in the whole blood.

(3) % ΔBV

It is the ratio of the blood volume change, and as shown in thefollowing formula, the ΔBV level at the time of measurement is dividedby BV₀ which is the BV level at the time of the initiation of dialysisand is expressed in percentage.ΔBV %=ΔBV/BV ₀×100(4) BV %

It is calculated by dividing the BV level at the time of measurement byBV₀ at the time of the initiation of dialysis and is expressed inpercentage.BV %=BV level at the time of measurement/BV ₀×1003. Definition of other Parameters of Blood and their Calculating Formula(1) Definition of PRR

PRR is an abbreviation for Plasma Refilling Rate, and is defined asspeed of the blood plasma refilling from the body to the blood vessel,and shows the patient's water removal ability at each point.

(2) Formula for calculating PRR

PPR is calculated with the following formula:PRR _(n) −UFR _(n) =ΔBV _(n) /T _(n)[wherein PRR_(n) is the Plasma Refilling Rate at an optional selectedmeasurement point (n), UFR_(n) is the water removal speed at an optionalselected measurement point (n), ΔBV_(n) is the blood volume change at anoptional selected measurement point' (n), T_(n) is the elapsed timeuntil an optional selected measurement point (n), and UFR is the waterremoval speed, respectively.]

Hereinafter, the target control line, the data line and the estimatedcontrol line used in the hemodialysis apparatus of the present inventionwill be explained.

The longitudinal axis of FIG. 2 is % ΔBV level, and the horizontal axisshows the elapsed time form the initiation of dialysis.

(1) Target Control Line:

It is shown by a hatched line A in the former part of the dialysis inFIG. 1 and in FIG. 2, and by a horizontal line D in the latter part ofdialysis. According to this target control line of FIG. 1, in the formerpart of the dialysis operation, a hemodialysis operation, for examplewater removal, which decreases the blood volume reasonably to the bodyis performed, and in the latter part of dialysis operation, a dialysisoperation, for example water removal, which maintains the blood volumesuitable to each patient according to the target control line, that is,to maintain the standard blood volume substantively constant isperformed. Therefore, this target control line is an indication of thechronological course or the chronological target level of the bloodindication level. In the meantime, said target control line is definedbefore hemodialysis by doctors and the like, and its angle of gradientis determined by the relation with the target water removal volume.

(2) Data Line and Estimated Control Line

It will be explained according to FIGS. 1 and 2. The data line B is theratio of the blood volume change composed with data level of the bloodindication level of % ΔBV_(1′), ΔBV_(2′) and the like. The estimatedcontrol line near by the target control line A is determined as follows:by using the blood indication level according to the measurement levelssuch as BV, ΔBV or % ΔBV and the like at the measurement point(controlling point); and the target blood indication level shown by saidtarget control line A at the next measurement point (controlling point),the dialysis conditions (for example, the water removal speed) to attainthe target blood indication level at the next measurement point(controlling point) is calculated, and the hemodialysis treatment iscarried out under this calculated dialysis conditions (for example, thewater removal speed), to attain the next measurement point (controllingpoint). As a result, the data line B which will likely slip away fromthe target control line A, will be corrected by the dialysis conditionsnewly defined at every measurement point (controlling point), andtherefore become the estimated control line C, which transits along saidtarget control line A.

(3) Deviated Control Line (Alarm Line) and Urgent Liquid Supply Line

The hatched line downward sloping shown beneath the target control linein the former part of the dialysis operation, and the horizontal line inthe latter part of the dialysis operation in FIG. 1, is the deviatedcontrol line (alarm line) E to function as a deviated control line(alarm line). Furthermore, the horizontal line defined under thedeviated control line (alarm line) E in the latter part of the dialysisoperation is the urgent liquid supply line F.

In case hemodialysis operation is carried out under the control of thehemodialysis apparatus of the present invention, in case the bloodindication level actually measured in the former and latter part of thedialysis operation exceeds said deviated control line (alarm line) E, itis preferable to adapt an emergency control, and for example in theformer part of the dialysis operation, it is preferable to adapt anemergency control different from the feed-forward control which usessaid target control line. For example, as it is shown in the graph inFIG. 1, in case the data line showing the transition of the data leveldeviates beneath the alarm line E, the water removal means such as waterremoval pump and the like should be stopped, or in case the data linedeviates beneath the urgent substitutive fluid supply line F, ifnecessary, a substitutive fluid replacement to the patient using a fluidreplacement pump is performed by priority before carrying out thecontrol by feed-forward.

As mentioned above, the hemodialysis apparatus of the present aspectdoes not only have the function to approach the blood indication levelto the target, but in case (the blood indication level is) deviated in adangerous region, it is possible to ensure the safety of the patient bypreferentially operating the emergency control. Moreover, the definedwater removal speed is shown in the bottom half of the graph in FIG. 1.

The hemodialysis apparatus of the present invention stops the waterremoval means such as water removal pump and the like by using saiddeviated control line (alarm line) E or urgent substitutive fluid supplyline F, or if necessary performs a substitutive fluid replacement to thepatient using a substitutive fluid replacement pump by priority, also inthe latter part of hemodialysis operation, as described above.Therefore, the hemodialysis apparatus of the present invention does notonly have the function to approach easily the primary blood volume (BV0)the standard blood volume in the former part of the dialysis operation,but in the former part of the dialysis operation and/or in the latterpart of the dialysis operation, in case (the blood indication level is)deviated in a dangerous region, it is possible to ensure the safety ofthe patient by preferentially operating the emergency control.

In the latter part of the dialysis operation, at the time that the waterremoval volume that was planned to be removed in the former part of thedialysis operation was removed, the water removal control of the latterpart of the dialysis operation is started. At this time, the waterremoval speed is calculated to finish removing the remaining waterremoval volume within the target water removal time, and the waterremoval is performed with said water removal speed. However, in casesaid water removal speed exceed the maximum water removal speed linedefined for the latter part of the dialysis operation, the hemodialysisis carried out with the maximum water removal speed, as for the formerpart of the dialysis operation.

INDUSTRIAL APPLICABILITY

By using the hemodialysis apparatus of the present invention, excellenteffects such as (1)–(3), as follows, can be obtained.

-   (1) The control mechanism is simple, and there is little risk of    misoperation or out-of-control.-   (2) As there is no need of difficult installation or unnecessary    operation, the operator can easily operate without difficulty.-   (3) As the control is carried out rapidly and finely, the blood    volume can be transited fairly during the hemodialysis.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a figure explaining the controlling method of the entire waterremoval operation of the blood treatment apparatus.

FIG. 2 is a figure showing the control in the former part of the waterremoval operation of the blood treatment apparatus.

FIG. 3 is a figure explaining the first calculating method of theprimary blood volume (BVo).

FIG. 4 is a figure explaining the second calculating method of theprimary blood volume (BVo).

In FIG. 1, (a) is the period performing only circulation outside thebody without performing water removal, (b) is the water removal periodat the time of the initiation of the water removal, (c), (d), (e), (f),(g), (h), (i), (j), (k), (l), (m), (n), (o) and (p) are water removalspeed determined with the use of said target control line, alarm line Eand maximum water removal line G or H, used in the corresponding period.In FIG. 2, % ΔBV_(1′), % ΔBV_(2′), % ΔBV_(3′), % ΔBV_(4′), and %ΔBV_(5′) are the ratio of the blood volume change measured at themeasurement point 1, 2, 3, 4 and 5; % ΔBV₁, % ΔBV₂, % ΔBV₃, % ΔBV₄, and% ΔBV₅ are the ratio of the blood volume change determined by the targetcontrol line at the measurement point 1, 2, 3, 4 and 5. Further, ΔT isthe interval of measurement time between each measurement point.Moreover, A is the control line (former part), B is the data line, C isthe estimated control line, D is the control line (latter part), E isthe deviated control line (alarm line), F is the urgent liquid supplyline, G is the maximum water removal speed line, and H is the maximumwater removal speed line, respectively.

BEST MODE OF CARRYING OUT THE INVENTION 1. EXAMPLE 1

The embodiments of control for hemodialysis operation of thehemodialysis apparatus of the present invention is explained accordingto FIG. 1. In the bottom half of FIG. 1, the defined water removal speedis shown.

As it is shown in FIG. 1, the maximum water removal speed line G and Hare defined in the former and latter part of the dialysis operation, inthe bottom half of FIG. 1, the defined water removal speed (or thehistory) in the former and latter part of the dialysis operation areshown.

Former Part of the Dialysis Operation

(1) Start of Dialysis

When starting dialysis, as the BV level is unstable, the water removalis not performed at the time of the initiation of dialysis (waterremoval speed is 0), only circulation outside the body is performed, andit is waited for the time interval to pass until the BV level stabilizes(period a). During the period a, the patient's primary blood level (BV₀)could be calculated according to the above (I).

(2) The Time of the Initiation of the Water Removal

After the BV value stabilizes, the hemodialysis apparatus is reset andthe measurement is started again. At this time, the patient's primaryblood level (BV₀) can be calculated according to the above (II), insteadof calculating the patient's primary blood level BV₀) according to theabove (I). The hemodialysis operation after the BV level is stabilized,the control of the water removal means by feed-forward control accordingto the above formula (n) of said target control line A was performed.Among the water removal speed (c)–(i) in the former part of thehemodialysis operation determined with the control method mentionedabove, the water removal speed d and h in the former part of thehemodialysis operation exceed the maximum water removal speed line G,therefore the maximum water removal speed is adapted. In the meantime,when the water removal speed exceeds the maximum water removal speedline, it is most preferable to adapt the maximum water removal speed assaid water removal speed, but it may be a water removal speed less thanthe maximum water removal speed. Moreover, as the data level of theblood volume or the blood volume change during dialysis at water removalspeed (f), becomes less than that of the alarm line, the water removalspeed is set f=0 (that is, water removal is not performed).

(3) Restart of the Water Removal

In the former part of the dialysis operation, when the blood volume orthe blood volume change becomes less than the alarm level, the waterremoval is stopped (water removal speed f=0), but when the blood volumeor the blood volume change exceeds the control line as a result of thetermination of water removal, the water removal is started again. As forthe primary water removal speed of the control at the time of startingagain, the water removal is performed with the water removal speedpredicated by the method mentioned above. At the time when the waterremoval volume predicted to be removed in the former part of thehemodialysis operation is removed and the standard blood volumeapproaches, or at the time when the ratio of the blood volume (% BV)becomes the object blood volume ratio (object % BV), the control ofwater removal of the latter part of hemodialysis operation is started.

Latter part of hemodialysis operation

The water removal speed is calculated to finish removing the remainingwater removal volume within the target water removal time, and the waterremoval is performed with said water removal speed. When performingwater removal with this water removal speed, the water removal isstopped in case the blood volume or the blood volume change becomes lessthan said alarm level. When the blood indication level attains downwardby exceeding the urgent liquid supply line defined beneath said deviatedcontrol line (alarm line), not only the working means that carries outblood treatment as mentioned above is stopped temporarily, but the bloodindication level is recovered rapidly to be above said deviated controlline (alarm line) by using the liquid supply means to inject liquidsupply inside the body together. For example, when the water removal isperformed with the water removal speed (j), the blood volume or theblood volume change became less than said alarm level. Therefore, thewater removal at the next controlling point is stopped, and the waterremoval speed (k) was set to 0.

Moreover, as a result of termination of said water removal, the actualblood volume change ΔBV level have been recovered to be above said alarmlevel, the water removal speed is calculated so that the remaining waterremoval volume at that controlling point is finished to be removedwithin the target water removal time (determined water removal volume),and the water removal is performed with said determined water removalspeed (1). By performing the water removal with said determined waterremoval speed (1), the actual ΔBV level becomes less than said alarmlevel again. Therefore, the water removal at the next controlling pointis stopped and the water removal speed (in) was set to 0. Furthermore,as a result of termination of said water removal, the actual ΔBV levelhave been recovered to be above the control line, the water removalspeed is calculated so that the remaining water removal volume at thatcontrolling point is finished to be removed within the target waterremoval time (determined water removal volume), and the water removal isperformed with said determined water removal speed (n). However, as saiddetermined water removal speed (n) exceeds the maximum water removalspeed line H, the maximum water removal speed was adapted as the actualwater removal speed. As the target water removal volume was not finishedto be removed by the end of the target water removal time, the waterremoval was performed with the maximum water removal speed up to thetarget removal volume, and the hemodialysis was finished.

1. A hemodialysis apparatus, comprising: means for measuring or calculating a blood volume or a blood volume change as a blood index level; a hemodialysis means; and a controlling means for controlling hemodialysis conditions of the hemodialysis means according to the blood index level, wherein the controlling means controls the hemodialysis means so that a hemodialysis operation is carried out without performing water removal when initiating the hemodialysis operation until the blood volume stabilizes, and the hemodialysis operation is carried out by performing water removal after the blood volume is stabilized by the hemodialysis operation, and wherein the controlling means enables calculation of a primary blood volume (BV₀) of an individual according the equation: (BV ₀)=increased blood volume circulating outside the body (space outside the body)/% ΔBV _(x), wherein % ΔBV_(x) is a ratio of the volume change of the blood volume (BV) when the hemodialysis operation is performed without performing water removal.
 2. A hemodialysis apparatus, comprising: means for measuring or calculating a blood volume or a blood volume change as a blood index level; a hemodialysis means; and a controlling means for controlling hemodialysis conditions of the hemodialysis means according to the blood index level, wherein the controlling means controls the hemodialysis means so that a hemodialysis operation is carried out without performing water removal when initiating the hemodialysis operation until the blood volume stabilizes, and the hemodialysis operation is carried out by performing water removal after the blood volume is stabilized by the hemodialysis operation, wherein the controlling means controls the hemodialysis means so that water removal is performed with a water removal speed A within ΔT (a time that a plasma refilling rate (PRR) does not change) when initiating the hemodialysis operation with water removal, and then to perform subsequently water removal with a water removal speed B which is different from the water removal speed A, within ΔT, and wherein the controlling means enables calculating the primary blood volume (BV₀) according to the equation: BV ₀=(water removal speed A−water removal speed B)/(−% ΔBV _(A) % ΔBV _(B))×ΔT, wherein % ΔBV_(A) is a ratio of the volume change of the blood volume (BV) when the water removal is performed with the water removal speed A and % ΔBV_(B) is a ratio of the volume change of the blood volume (BV) when the water removal is performed with the water removal speed B. 